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Biomedical subjects

C Cheng

Publications and source records attributed to C Cheng.

At least 127 records · Page 7Linked to original sources
PubMed1997

Near nerve local insulin prevents conduction slowing in experimental diabetes.

Insulin may have direct effects on axons through its actions on insulin receptors or through cross occupancy of insulin-like growth factor-1 receptors. We tested the hypothesis that insulin itself influences conduction of myelinated fibers independent of hyperglycemia in experimental diabetes. Low dose intermittent (0.2 units thrice weekly) Toronto (regular) insulin was injected at the sciatic notch and knee near the left sciatic nerve of rats rendered diabetic with citrate buffered streptozotocin or nondiabetic rats given citrate only. Identical volumes of normal saline were injected near the contralateral right sciatic nerve. The diabetic rats developed hyperglycemia, elevated glycosylated hemoglobin levels and had slowing of right (saline treated) sciatic tibial motor and caudal sensory conduction velocity. In contrast, local insulin treatment on the left side prevented conduction slowing, unilaterally increasing conduction velocity. In nondiabetic rats, conduction velocities were slightly higher on the insulin treated side, but the influence of insulin was less robust than in diabetics. The insulin treated sural branches of the sciatic nerves in diabetics had a higher percentage of small (< or = 9.0 microm diameter) myelinated fibers than the saline treated nerves. Local insulin has a trophic influence on myelinated fibers that is prominent in diabetic nerves and is independent of hyperglycemia.

Animals↗
PubMed1997

Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom.

BACKGROUND: Chinese men have lower incidences of prostate cancer compared to men from Europe and North America. Asians consume large quantities of soya, a rich source of isoflavanoids phyto-oestrogens and have high plasma and urinary levels of these compounds. The mammalian lignans, enterolactone and enterodiol, are another group of weak plant oestrogens and are derived from seeds, cereals and grains. Vegetarians have high plasma and urinary concentrations of lignans. METHODS: The concentrations lignans and isoflavonic phyto-oestrogens were determined by gas chromatography-mass spectrometry (GC-MS) in plasma and prostatic fluid from Portuguese, Chinese and British men consuming their traditional diets. RESULTS: In prostatic fluid the mean concentrations of enterolactone were 31, 162 and 20.3 ng/ml for Hong Kong, Portugal and Britain respectively. Very high levels of enterolactone (> 600 ng/ml) were observed in the prostatic fluid of some of the men from Portugal. High concentrations of equol (3270 ng/ml) and daidzein (532 ng/ml) were found in a sample of prostatic fluid from Hong Kong. Higher mean levels of daidzein were observed in prostatic fluid from Hong Kong at 70 ng/ml, compared to 4.6 and 11.3 ng/ml in samples from Portugal and Britain respectively. Mean levels of daidzein were higher in the plasma samples from Hong Kong (31.3 ng/ml) compared to those from Portugal (1.3 ng/ml) and Britain (8.2 ng/ml). In general, the mean plasma concentrations of enterolactone from the three centres were similar, at 6.2, 3.9 and 3.9 ng/ml in samples from Hong Kong Portugal and Britain respectively. CONCLUSIONS: Higher concentrations of the isoflavanoid phyto-oestrogens, daidzein and equol, were found in the plasma and prostatic fluid of men from Hong Kong compared to those from Britain and Portugal. However, the levels of the lignan, enterolactone, were very much higher in prostatic fluid of Portuguese men. Isoflavanoids and lignans have many interesting properties and may, in part, be responsible for lower incidences of prostate cancer in men from Asia and also some Mediterranean countries. The isoflavanoids from soya, which are present in high concentrations in the prostatic fluid of Asian men, may be protective against prostate disease.

4-Butyrolactone↗
PubMed1997

Kinetic analysis of DNA and RNA strand transfer reactions catalyzed by vaccinia topoisomerase.

Vaccinia topoisomerase binds duplex DNA and forms a covalent DNA-(3'-phosphotyrosyl) protein adduct at the sequence 5'-CCCTT downward arrow. The enzyme reacts readily with a 36-mer CCCTT strand (DNA-p-RNA) composed of DNA 5' and RNA 3' of the scissile bond. However, a 36-mer composed of RNA 5' and DNA 3' of the scissile phosphate (RNA-p-DNA) is a poor substrate for covalent adduct formation. Vaccinia topoisomerase efficiently transfers covalently held CCCTT-containing DNA to 5'-OH-terminated RNA acceptors; the topoisomerase can therefore be used to tag the 5' end of RNA in vitro. Religation of the covalently bound CCCTT-containing DNA strand to a 5'-OH-terminated DNA acceptor is efficient and rapid (krel > 0.5 s-1), provided that the acceptor DNA is capable of base pairing to the noncleaved DNA strand of the topoisomerase-DNA donor complex. The rate of strand transfer to DNA is not detectably affected by base mismatches at the 5' nucleotide of the acceptor strand. Nucleotide deletions and insertions at the 5' end of the acceptor slow the rate of religation; the observed hierarchy of reaction rates is as follows: +1 insertion > -1 deletion > +2 insertion >> -2 deletion. These findings underscore the importance of a properly positioned 5'-OH terminus in transesterification reaction chemistry, but they also raise the possibility that topoisomerase may generate mutations by sealing DNA molecules with mispaired or unpaired ends.

Catalysis↗
PubMed1997

Inhibition of nitric oxide synthase enhances peripheral nerve regeneration in mice.

We tested the hypothesis that inhibition of nitric oxide synthase (NOS) following transection of the sciatic nerve in the mouse would adversely influence regeneration of myelinated fibers from the proximal stump. NOS was inhibited by N(omega)-nitro-L-arginine-methyl ester (L-NAME; 10 mg/kg i.p.), a broad spectrum NOS inhibitor given twice daily for the first 10 days following nerve transection in Swiss mice. Controls received the inactive enantiomer N(omega)-nitro-D-arginine methyl ester (D-NAME). Regeneration was assessed by serial recordings of the M potential from interosseous muscles of the foot innervated by sciatic-tibial motor fibers and morphometric analysis of myelinated fibers distal to the injury site. Contrary to expectation, M potentials reappeared earlier in the mice treated with L-NAME and were higher in amplitude (reflecting the number of reinnervating motor fibers) at 10 weeks after the injury. In the L-NAME treated mice, the mean axonal diameter of regenerating tibial myelinated fibers was larger and the fiber size histogram was shifted to larger fibers. Inhibition of NOS in a transected peripheral nerve is associated with enhanced regeneration of myelinated fibers. Local elaboration of NO may be toxic to regenerating axons.

Animals↗
PubMed1997

Characterization of an ATP-dependent DNA ligase encoded by Haemophilus influenzae.

We report that Haemophilus influenzae encodes a 268 amino acid ATP-dependent DNA ligase. The specificity of Haemophilus DNA ligase was investigated using recombinant protein produced in Escherichia coli. The enzyme catalyzed efficient strand joining on a singly nicked DNA in the presence of magnesium and ATP (Km = 0.2 microM). Other nucleoside triphosphates or deoxynucleoside triphosphates could not substitute for ATP. Haemophilus ligase reacted with ATP in the absence of DNA substrate to form a covalent ligase-adenylate intermediate. This nucleotidyl transferase reaction required a divalent cation and was specific for ATP. The Haemophilus enzyme is the first example of an ATP-dependent DNA ligase encoded by a eubacterial genome. It is also the smallest member of the covalent nucleotidyl transferase superfamily, which includes the bacteriophage and eukaryotic ATP-dependent polynucleotide ligases and the GTP-dependent RNA capping enzymes.

Adenine↗
PubMed1997

Mutational analysis of 39 residues of vaccinia DNA topoisomerase identifies Lys-220, Arg-223, and Asn-228 as important for covalent catalysis.

Vaccinia DNA topoisomerase, a 314-amino acid type I enzyme, catalyzes the cleavage and rejoining of DNA strands through a DNA-(3'-phosphotyrosyl)-enzyme intermediate. To identify amino acids that participate in the transesterification reaction, we introduced alanine substitutions at 39 positions within a conserved 57amino acid segment upstream of the active-site tyrosine. Purified wild type and mutant proteins were compared with respect to their activities in relaxing supercoiled DNA. The majority of mutant proteins displayed wild type topoisomerase activity. Mutant enzymes that relaxed DNA at reduced rates were subjected to kinetic analysis of the strand cleavage and religation steps under single-turnover and equilibrium conditions. For the wild type topoisomerase, the observed single-turnover cleavage rate constant (kcl) was 0.29 s-1 and the cleavage-religation equilibrium constant (Kcl) was 0.22. The most dramatic mutational effects were seen with R223A; removal of the basic side chain reduced the rates of cleavage and religation by factors of 10(-4.3) and 10(-5.0), respectively, and shifted the cleavage-religation equilibrium in favor of the covalently bound state (Kcl = 1). Introduction of lysine at position 223 restored the rate of cleavage to 1/10 that of the wild type enzyme. We conclude that a basic residue is essential for covalent catalysis and suggest that Arg-223 is a constituent of the active site. Modest mutational effects were observed at two other positions (Lys-220 and Asn-228), at which alanine substitutions slowed the rates of strand cleavage by 1 order of magnitude and shifted the equilibrium toward the noncovalently bound state. Arg-223 and Lys-220 are conserved in all members of the eukaryotic type I topoisomerase family; Asn-228 is conserved among the poxvirus enzymes.

Amino Acid Sequence↗
PubMed1997

Measurement and metabolism of isoflavonoids and lignans in the human male.

Asian men, who consume a low fat/high fibre soya-based diet, have very much lower incidence of prostate cancer than men from North America and Europe. The soya bean is a rich source of the isoflavonic phyto-oestrogens, daidzein, genistein and equol, compounds which may be cancer-protective in Asian populations. The lignans, enterolactone and enterodiol, plant oestrogens derived from cereals and vegetables, may act in a similar manner in vegetarian men. We report here on the measurement of isoflavonoids and lignans, by gas chromatography-mass spectrometry, in prostatic fluid of men from Asia and Europe and also on the metabolism of these compounds in Western men following dietary supplementation.

Adult↗
PubMed1997

Yeast PIG genes: PIG1 encodes a putative type 1 phosphatase subunit that interacts with the yeast glycogen synthase Gsy2p.

The biosynthesis of glycogen involves multiple proteins that associate with each other and the glycogen macromolecule. In efforts to understand the nature of these proteins, a two-hybrid screen was undertaken to detect proteins able to interact with Gsy2p, a major form of glycogen synthase in Saccharomyces cerevisiae. Two positives expressed proteins derived from genes designated PIG1 and PIG2, on chromosomes XIIR and IXL respectively. PIG1 codes for a protein with 38% identity over a 230 residue segment to Gac1p, a protein thought to be a type 1 protein phosphatase targeting subunit whose loss impairs glycogen synthesis. Pig2p has 30% identify to the protein corresponding to an open reading frame, YER054, on chromosome V. Deletion of PIG1 on its own had little effect on glycogen storage but, in combination with loss of GAC1, caused a more severe glycogen-deficient phenotype than seen in gac1 mutants. This result is consistent with Pig1p being functionally related to Gac1p and we propose that Pig1p may be a type 1 phosphatase regulatory subunit. Delection of PIG2, YER054, or both genes together caused no detectable change in glycogen metabolism under the conditions tested. Gac1p, Pig1p, Pig2p and the YER054p are the only four proteins coded by the yeast genome that share a conserved segment of approximately 25 residues, designated the GVNK motif, that is identifiable also in RGI, the mammalian type 1 phosphatase targeting subunit.

Amino Acid Sequence↗
PubMed1997

Peptides and neuromas: calcitonin gene-related peptide, substance P, and mast cells in a mechanosensitive human sural neuroma.

We examined and compared a mechanosensitive human sural neuroma and a contralateral sural nerve collected simultaneously from a patient involved in a diabetic neuropathy research protocol. Using indirect immunofluorescence staining. we identified a striking difference in the content within axons of two neuropeptides, substance P (SP) and calcitonin, gene-related peptide (CGRP), between the contralateral nerve and the neuroma. Unlike the contralateral nerve, where immunofluorescence was sparse, a significant number of disorganized axon profiles that stained brightly positive for CGRP or SP were identified in the neuroma. In contrast, staining for tyrosine hydroxylase, a label of sympathetic axons, was largely absent except around one large arteriole. The neuroma specimen also contained large numbers of serotonin-containing mast cells, only noted occasionally in the contralateral nerve. The peptide staining and mast cell accumulation in the human neuroma closely resembled changes we have previously observed in an animal neuroma model. Local neuropeptides may play a role in the injury response of peripheral nerve, and may be related to mechanosensitivity.

Antibody Specificity↗
PubMed1997

Machado-Joseph disease: clinical, molecular, and metabolic characterization in Chinese kindreds.

Machado-Joseph disease, an autosomal dominant multisystem motor degeneration, has been described mainly in people of Portuguese descent. Our report documents the presence of Machado-Joseph disease in the Chinese population, based on the specific molecular marker of a CAG repeat array in the 3' end of the MJD gene. We screened 21 Chinese families with dominant spinocerebellar ataxia. The results showed that Machado-Joseph disease with CAG expansion accounted for 52% of families with autosomal dominant cerebellar ataxia in this series. The clinical characteristics, besides the well-documented cerebellar ataxia, dysarthria, nystagmus, corticospinal dysfunctions, a variable degree of facial muscle fasciculation, and proprioceptive loss, included loss of optokinetic nystagmus and autonomic nervous system dysfunction. The CAG repeat number in the MJD gene ranged from 14 to 39 among normal alleles, and from 63 to 81 among MJD alleles. There was a strong inverse correlation (gamma = -0.77) between number of CAG repeats and age at symptom onset, accounting for 60% of the variance of age at onset. A strong clinical anticipation of age at onset existed in successive generations. Mild instabilities of expanded CAG repeat numbers during meiotic transmission occurred, with no significant difference according to the gender of the transmitting parent. Finally, brain metabolism in Machado-Joseph disease, studied with positron emission tomography, was characterized by significant progressive regional hypometabolism in the occipital cortex, as well as the cerebellar hemispheres, vermis, and brainstem.

Adult↗
PubMed1997

Assessment of major life events for Hong Kong adolescents: the Chinese Adolescent Life Event Scale.

Previous Chinese research on adolescent life stress adopted life event scales that were directly translated from Western measures. To address the methodological and cultural issues overlooked by the "import" approach, the present research aimed at constructing a life event scale for Hong Kong adolescents. Study 1 was conducted to congregate items for the Chinese Adolescent Life Event Scale (CALES). The CALES contains 44 items derived from 618 Hong Kong adolescents. Study 2 revealed adequate test-retest reliability and criterion-related validity for the CALES. Moreover, the CALES yielded stronger relationships with depression than did the translated life event measures. Results suggest that the CALES is appropriate for assessing life events for Hong Kong adolescents. Both unique features of the CALES and life events found only in the translated measures are examined. Implications for Chinese research on life stress are discussed.

Adolescent↗
PubMed1997

A comparative study of the distribution of ofloxacin and ciprofloxacin in prostatic tissues after simultaneous oral ingestion.

OBJECTIVES: To determine the levels of two quinolones, ofloxacin and ciprofloxacin, potent broad-spectrum antibiotics with very good oral bioavailability and low minimum inhibitory concentrations (MICs) for most pathogens, in the prostates of patients who underwent transurethral resection of the prostate (TURP) after oral ingestion for surgical prophylaxis. PATIENTS AND METHODS: Twenty-eight patients with BPH requiring a TURP ingested 250 mg of both drugs 2-4 h before operation. The levels of the drugs in the serum and prostate were measured using high-performance liquid chromatography and the levels of both drugs determined at the 6 and 9 o'clock positions in the prostate to examine any local variations in drug concentration. RESULTS: Ofloxacin concentrations were significantly higher in the serum and prostatic tissues compared with ciprofloxacin for the same dose, but its penetrance into the prostate was lower. This mainly reflected its higher oral bioavailability. Both drugs were present in concentrations 50% higher at the 6 o'clock than at the 9 o'clock position but both exceeded the MICs for most Gram-negative organisms except Pseudomonas. CONCLUSION: Ofloxacin has the advantage against ciprofloxacin of exceeding the MICs for Staphylococcus and Chlamydia. However, ciprofloxacin has the advantage of having prostate-to-serum ratios of unity, but for the same dose the prostatic concentrations of ofloxacin is significantly higher.

Administration, Oral↗
PubMed1997

Neutralizing human monoclonal antibodies to conformational epitopes of human T-cell lymphotropic virus type 1 and 2 gp46.

Ten human monoclonal antibodies derived from peripheral B cells of a patient with human T-cell lymphotropic virus (HTLV)-associated myelopathy are described. One monoclonal antibody recognized a linear epitope within the carboxy-terminal 43 amino acids of HTLV gp21, and two monoclonal antibodies recognized linear epitopes within HTLV type 1 (HTLV-1) gp46. The remaining seven monoclonal antibodies recognized denaturation-sensitive epitopes within HTLV-1 gp46 that were expressed on the surfaces of infected cells. Two of these antibodies also bound to viable HTLV-2 infected cells and immunoprecipitated HTLV-2 gp46. Virus neutralization was determined by syncytium inhibition assays. Eight monoclonal antibodies, including all seven that recognized denaturation-sensitive epitopes within HTLV-1 gp46, possessed significant virus neutralization activity. By competitive inhibition analysis it was determined that these antibodies recognized at least four distinct conformational epitopes within HTLV-1 gp46. These findings indicate the importance of conformational epitopes within HTLV-1 gp46 in mediating a neutralizing antibody response to HTLV infection.

Antibodies, Monoclonal↗
PubMed1997

[Studies on biological effects of kappa-selenocarrageenan on human breast cancer cell line BCaP-37].

Proliferation, cell cycle, total amount of DNA, area of cell nucleus, as well as epidermal growth factor receptors (EGFR) and expression of oncogene C-erbB2 mRNA of Chinese breast cancer cell line (BCaP-37) after being treated with kappa-selenocarrageenan were determined by cell culture technique, image cytometry (ICM) and northern blot to explore its anti-tumor mechanism. Results revealed 3.0-120 mg/L selenocarrageenan could inhibit proliferation of BCaP-37, with a response of time and dose dependence. The areas of nuclei were significantly lower with ICM in cells treated with 15 or 60 mg/L selenocarrageenan for four days than those in controls (P < 0.01). Levels of EGFR and expression of C-erbB2 mRNA were significantly inhibited in cells treated with 60 mg/L selenocarrageenan. It suggests that selenocarrageenan can inhibit proliferation of breast cancer cells through regulation of the levels of EGFR and expression of C-erbB2 mRNA.

Antineoplastic Agents↗
PubMed1996

Initiation of glycogen synthesis in yeast. Requirement of multiple tyrosine residues for function of the self-glucosylating Glg proteins in vivo.

The self-glucosylating proteins, Glg1p and Glg2p, are required for glycogen synthesis in Saccharomyces cerevisiae (Cheng, C., Mu., J., Farkas, I., Huang, D., Goebl M. G., and Roach, P. J. (1995) Mol. Cell. Biol. 15, 6632-6640). Glg2p was shown to be associated with carbohydrate in vivo and was released from the high molecular weight glycogen fraction by treatment with alpha-amylase. In addition, some Glg2p exists as a protein of Mr approximately 43,000, whose proportion is increased in cells lacking glycogen synthase. Unlike the mammalian counterpart, glycogenin, the yeast Glg proteins appear to require multiple Tyr residues for functionality. In Glg2p, mutation of both Tyr230 and Tyr232 is necessary to suppress self-glucosylation of purified protein in vitro. The mutant protein is still capable of transferring glucose to an exogeneous acceptor, n-dodecyl beta-D-maltoside. A small COOH-terminal region, conserved between Glg1p and Glg2p, is also important for function; mutation of Tyr367 or truncation at residue 362 impairs the ability of primed Glg2p to be elongated by glycogen synthase. Complete suppression of glycogen accumulation in vivo requires mutation of all three Tyr residues. In Glg1p, two Tyr residues are implicated, Tyr232 and Tyr600, mutation of both being required to eliminate glycogen accumulation in vivo.

Amino Acid Sequence↗
PubMed1996

Thermoregulation and heart rate variability.

1. Heart rate variability is modulated by multiple control systems, including autonomic and hormonal systems. Long-term variability, i.e. the very low-frequency band of the power spectra, has been postulated to reflect thermoregulatory vasomotor control, based upon thermal entrainment experiments. However, the relationship between thermoregulatory responses (vasoconstriction and shivering) and heart rate variability has not been studied. 2. We performed two distinct protocols in a series of human subjects. In the first protocol, core temperature was reduced by intravenous infusion of cold saline, while skin temperature was unchanged. The second protocol involved skin-surface warming and cooling until shivering developed. Power spectral analysis was performed using a fast Fourier transformation, and the area in three distinct band-widths was determined. 3. Very low-frequency power (0.0039-0.04 Hz) increased significantly in response to core cooling, peripheral vasoconstriction and shivering, while both very low- and low- (0.04-0.15 Hz) frequency power increased in response to skin-surface cooling. Heart rate decreased during core cooling-induced vasoconstriction, suggesting a direct thermal response, and increased in relation to the metabolic demands associated with shivering. 4. Our results suggest that very low-frequency power is modulated by thermal stimuli which result in core hypothermia and thermoregulatory activity, while skin-surface cooling without core hypothermia does not selectively modulate this frequency band.

Adult↗
PubMed1996

Staurosporine induces a sequential program of mouse keratinocyte terminal differentiation through activation of PKC isozymes.

Staurosporine (stsp) induces assembly of cornified envelopes in mouse keratinocyte cultures. To clarify whether this effect is the consequence of a coordinated differentiation program similar to that observed in epidermis, we assessed the expression of multiple differentiation-specific markers in stsp-treated keratinocytes. In medium containing 0.05 mM Ca2+, in which the basal cell phenotype is normally maintained, stsp induced dose-dependent increases in keratin 1, epidermal and keratinocyte transglutaminases, SPR-1, loricrin, and profilaggrin mRNA. Based on nuclear run-on analysis, stsp-mediated marker expression was found to be due at least in part to increased transcription. Since protein kinase C (PKC) activation is required for keratinocyte differentiation, we tested whether stsp influenced this signaling pathway. Stsp induced the translocation of multiple PKC isoforms from the cytosol to membrane and/or cytoskeletal fractions, inducing isozyme downregulation within 24 h. Moreover, AP-1 DNA binding activity was elevated in stsp-treated keratinocytes, consistent with the notion that this agent influences keratinocyte-specific gene expression via the PKC pathway. Stsp-mediated marker expression was inhibited by the PKC inhibitor GF 109203X. In cells pre-treated with bryostatin 1 to selectively down-modulate specific PKC isoforms, stsp-induced loricrin, filaggrin, and SPR-1 expression was suppressed when PKC alpha, epsilon, and/or delta were downregulated, suggesting that these isozymes may be necessary for marker expression in response to this agent. Thus, in addition to its effects on cornified envelope assembly, stsp induces a coordinate program of differentiation-specific keratinocyte gene expression that is mediated at least in part by the PKC signaling pathway.

Alkaloids↗